Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels.Nevertheless,the mech-anism responsible for this dynamic insulin secretion has not been completely understood,particularly a...Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels.Nevertheless,the mech-anism responsible for this dynamic insulin secretion has not been completely understood,particularly at the single islet level.In this study,we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion(GSIS)at the single islet level.With the utilization of this platform,we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats.Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS:Type Ⅰ exhibits a biphasic GSIS profile with a fast first phase and flat second phase;Type Ⅱ also has a biphasic GSIS profile with a fast first phase but a slow increased second phase;Type Ⅲ displays only a slowly increased second phase and lacks a fast first phase.RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets,respectively.Moreover,our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion.Furthermore,we revealed that diabetic islets exhibit only the type Ⅰ GSIS response,indicating a deliberate impairment of the second phase of insulin secretion.Together,this device serves as a crucial tool in the research field of islets and diabetes,allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.展开更多
基金the financial supports from the National Key Research and Development Program of China(2020YFA0908200,2021YFA1101300)China Postdoctoral Science Foundation(2021M703418)technique support from Advanced Cell Technology Core facility and Imaging Core facility.
文摘Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels.Nevertheless,the mech-anism responsible for this dynamic insulin secretion has not been completely understood,particularly at the single islet level.In this study,we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion(GSIS)at the single islet level.With the utilization of this platform,we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats.Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS:Type Ⅰ exhibits a biphasic GSIS profile with a fast first phase and flat second phase;Type Ⅱ also has a biphasic GSIS profile with a fast first phase but a slow increased second phase;Type Ⅲ displays only a slowly increased second phase and lacks a fast first phase.RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets,respectively.Moreover,our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion.Furthermore,we revealed that diabetic islets exhibit only the type Ⅰ GSIS response,indicating a deliberate impairment of the second phase of insulin secretion.Together,this device serves as a crucial tool in the research field of islets and diabetes,allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.
